DESCRIPTION (the applicant's description verbatim): Most episodes of sudden cardiac death are caused by ventricular fibrillation (VF). Electrical defibrillation is the only practical means for halting VF. The best way to improve defibrillation is to understand the basic mechanisms by which shocks cause a change in transmembrane potential (dVm) and how this dVm halts the activation fronts of VF. Progress has been made recently in understanding these mechanisms. Some of this progress has been made using electrical mapping to record activation in 3 dimensions plus the distribution of potentials created through the heart by shock and using optical mapping to obtain an estimate of the action potentials and dVm. These advances have raised many new questions. This application proposes to investigate the mechanisms of defibrillation using electrical mapping in dogs and optical mapping in isolated, perfused rabbit hearts. Two types of optical recording systems will be used: a photodiode array to study a small epicardial region with high temporal and dVm resolution and video cameras to obtain a global picture of the entire ventricular epicardium. There are four specific aims, each of which is to answer a question that is crucial for understanding how a shock defibrillates. 1. What are the distribution and magnitude of dVm in the ventricles during a shock? 2. What causes dVm during the shock? 3. How does this dVm generate new action potentials and action potential prolongation? 4. What determines if the post-shock activation regenerates VF? The following four hypotheses will be tested, each of which corresponds to a specific aim. 1. Large regions (mm to cm) of dVm are present over the entire epicardium, including regions far from the defibrillation electrodes. 2. Two types of effects, bidomain and secondary source, are both responsible for dVm caused by shocks, with bidomain effects predominating in normal hearts and secondary source effects becoming more important in diseased hearts. 3. Activation following the shock arises by two different mechanisms: propagation away from the border of a directly activated region sometimes forming reentrant pathways and propagation centrifugally away from a focus. 4. The primary determinant of the success or failure of shocks near the defibrillation threshold in normal hearts is not the global dispersion of refractoriness immediately after the shock, but is the number and rapidity of post-shock organized cycles of activation, while in diseased hearts the dispersion of refractoriness becomes an important determinant of defibrillation outcome.